Advertisement

Advertisement

Science : The genes of the fathers . . .

By Gail Vines

A REVOLUTIONARY technique that allows infertile men to have children may
threaten the fertility of their sons, say researchers.

The technique, known as intracytoplasmic sperm injection (ICSI), involves
injecting a single sperm directly into a mature egg. Even immature sperm that
have been removed artificially from the testicles can achieve fertilisation if
introduced into the egg in this way, allowing men with low sperm counts or with
immobile or misshapen sperm to become fathers.

Introduced in 1992, ICSI was widely regarded as a breakthrough in the
treatment of male infertility, which is the problem for an estimated 40 per cent
of infertile couples. The technique is now available in leading fertility
clinics throughout Europe and North America.

However, because it involves forcing a single sperm directly into the egg,
fears are growing that it risks passing on genetic abnormalities to future
generations. Other in vitro methods allow “natural” contact between sperm and
egg, making it more difficult for unhealthy sperm to achieve fertilisation. But
ICSI removes this natural barrier. Moreover, men selected for ICSI are likely to
be infertile for genetic reasons.

Advertisement

Earlier this year, David Page of the Massachusetts Institute of Technology in
Cambridge and his colleagues discovered that a gene was missing from the Y
chromosome of men with very low sperm counts (The Lancet, vol 347, p
1290). Page says deletions in this gene, called the azoospermia factor (AZF),
could be transmitted by ICSI and “would probably result in infertile sons …
It may be appropriate to offer Y-DNA testing and genetic counselling before
starting assisted reproductive procedures.”

Ann Chandley of the Medical Research Council’s Human Genetics Unit in
Edinburgh and Tim Hargreaves of the Western General Hospital in Edinburgh have
recently launched a worldwide study to look for gene mutations on the Y
chromosomes of ICSI fathers and sons. Chandley warns: “Some clinics, especially
on the continent, seem to be racing away with ICSI technology, without much
regard of what the consequences for the baby might be in genetic terms. Nature
has a way of trying to clean up the germ line, and not allow sperm with genetic
anomalies through to fertilise the egg. In ICSI, all the hurdles are eliminated
at one go.” She believes there should be more genetic testing of potential
fathers before ICSI is carried out.

Up to now, scientists had assumed that ICSI was safe. Most studies have found
no increase in malformations in babies born using the technique. But there are
now fears that genetic disorders could be waiting in the wings, only becoming
apparent long after birth, in childhood or adulthood.

Earlier this month, the Health Council of The Netherlands called for
long-term studies of ICSI children. It also called for more research on animals
to test the safety of ICSI over several generations. “The technique was
introduced into clinical use without thorough testing in animals,” claims Juriy
Wladimiroff, professor of genetics and gynaecology at Erasmus University in
Rotterdam.